This application requests funding for an electron microscope (EM) and a CCD camera for direct acquisition of digital images. At present the EM Facility has two microscopes which have been running continuously since 1979 and 1984. Because both instruments represent outdated technology and replacement parts are becoming scarce or unavailable, their present utility to investigators at Fox Chase Cancer Center (FCCC) is clearly sub-optimal. The research interests of the 13 NIH funded FCCC investigators who will be the main users of the EM, vary widely. Most of the investigators have carried out preliminary analyses using standard light and fluorescent microscopy techniques. The requested equipment was chosen based upon the diversity of these research interests, with the goal of satisfying the investigators' immediate and long term needs. The research programs described in this application are aimed at understanding human cancer and other disease processes. This will be accomplished through EM studies of ultrastructure and the intracellular localization and trafficking of biologically important molecules including chromatin, structures critical to the regulation of DNA replication, cytokinesis, and meiosis, products of oncogene and tumor suppressor genes, and viral components. Among the proposed projects are study of the progression of chronic hepatitis to malignancy in liver cells and elucidation of the function of recently characterized tumor suppressors. The analysis of the mechanisms of nuclear import of retroviral proteins is pertinent to both cancer and AIDS. Aspects of the control of cell cycle and the cell division studied in several others projects will provide information relevant to basic mechanisms of cancer. All of these projects share a need for ultrastructural analyses provided by EM. The requested system will be housed and operated by the EM Core Facility at FCCC. This shared facility has an ideal location in a central laboratory wing and serves the majority of NIH funded laboratories at FCCC. Highly trained and motivated staff will assist the managerial and scientific components of this application in a manner which should be ideally suited to a shared resource facility.